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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 1,081 records · Page 60Linked to original sources

Danazol binding to steroid receptors in human uterine endometrium.

To understand the mechanism of action of danazol, the binding of danazol to multiple classes of intracellular steroid binding proteins was studied in the human uterine endometrium. Danazol bound to endometrial receptors for estrogen, progesterone, and androgen and seemed to bind to endometrial intracellular corticosteroid-binding globulin and sex-hormone-binding globulin. Danazol occupies almost all binding sites of steroids in the steroid target cells in spite of the presence of endogenous steroids. It is speculated that the binding behavior of danazol may be related to its therapeutic effect on endometriosis.

Binding Sites↗

Pyridonecarboxylic acids as antibacterial agents. 4. Synthesis and antibacterial activity of 7-(3-amino-1-pyrrolidinyl)-1-ethyl-6-fluoro-1,4 -dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid and its analogues.

The title compounds (28-56) with an amino- and/or hydroxy-substituted cyclic amino group at C-7 were prepared with 1-substituted 7-chloro-, 7-(ethylsulfonyl)-, and 7-(tosyloxy)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3- carboxylic acids and their ethyl esters (3-7) with cyclic amines such as 3-aminopyrrolidine. The N-1 substituent includes ethyl, vinyl, and 2-fluoroethyl groups. As a result of in vitro and in vivo antibacterial screenings, three compounds, 1-ethyl- and 1-vinyl-7-(3-amino-1-pyrrolidinyl)-6-fluoro- 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids (33a and 33b) and 1-vinyl-7-[3-(methylamino)-1-pyrrolidinyl] analogue 34b, were found to be more active than enoxacin (2) and to be worthy of further biological study. Structure-activity relationships are discussed.

Anti-Bacterial Agents↗

Protoplast Fusion of Trichoderma reesei, Using Immature Conidia.

Protoplast fusion of strains derived from Trichoderma reesei QM9414 and QM9136 and the segregation of the resulting fusants were studied. Combinations of protoplasts prepared from young conidia with double amino acid requirements, one of which was a common requirement and the other uncommon, were fused in the presence of polyethylene glycol 6000. Fusants were selected as regenerant colonies requiring only the commonly deficient amino acid. The frequency of fusion was 0.9 x 10 to 4.0 x 10 for the starting conidia and 3.0 x 10 to 4.9 x 10 for the regenerated protoplasts, which was significantly higher than the expected reversion frequencies by mutation. Conidia generated on the fusant colonies showed diverse phenotypes, i.e., parental types (40 to 80%) and nonparental types (20 to 60%). Colonies developed from single conidia of the nonparental phenotype contained special spots called "knobs" that have a higher density of mycelia. The phenotype of the knobs was again varied among prototrophs, parental types, and recombinant types; and their traits were inherited stably. The phenotype of the mycelia in the nonknob part was essentially the same as that of the original conidia and again formed knobs in colonies upon transfer of a piece of mycelia to a fresh medium. The conidial DNA content of the knob clone was almost the same as that of the parents, but that of the fusants was 1.2 to 2.0 times higher than that of the parents. From these results, we conclude that knobs are the segregants from the fusants. One knob clone showed twice the carboxymethyl cellulose hydrolyzing activity of the parents, suggesting the possibility of breeding T. reesei cells by the protoplast fusion technique.

Journal Article↗

DNA-DNA hybridization analysis of nylon oligomer-degradative plasmid pOAD2: identification of the DNA region analogous to the nylon oligomer degradation gene.

Fine structure of the gene of 6-aminohexanoic acid cyclic dimer hydrolase, one of the enzymes responsible for the degradation of the nylon oligomer (6-aminohexanoic acid cyclic dimer), on the plasmid pOAD2 harbored in Flavobacterium sp. KI72 was determined by constructing miniplasmids from plasmid pNDH5 (a hybrid plasmid consisting of pBR322 and a 9.1-kilobase-pair HindIII fragment of pOAD2 ). The 6-aminohexanoic acid cyclic dimer hydrolase produced by cells of Escherichia coli C600 harboring pNDH5 or its miniplasmid was examined immunologically and electrophoretically and was found to be identical to that of Flavobacterium sp. KI72 . A fragment of pOAD2 (17.2- to 19.1-kilobase-pair region on pOAD2 ) was detected as hybridized fragment by Southern blotting experiments, indicating the presence of the DNA region analogous to the 6-aminohexanoic acid cyclic dimer hydrolase gene on the plasmid.

Amidohydrolases↗

Molecular basis of isozyme formation of beta-galactosidases in Bacillus stearothermophilus: isolation of two beta-galactosidase genes, bgaA and bgaB.

Bacillus stearothermophilus IAM11001 produced three beta-galactosidases, beta-galactosidase I, II, and III (beta-gal I, II, and III), which are detectable by polyacrylamide (nondenatured) gel electrophoresis. By connecting restriction fragments of the chromosomal DNA to plasmid vectors, followed by transformation of Escherichia coli, two beta-galactosidase genes (bgaA and bgaB) located close to each other on the chromosome were isolated. Identification of the gene products and Southern hybridization analyses with a 2.7-kilobase-pair EcoRI fragment containing the bgaA gene as probe revealed that a single bgaA gene exists on the genome and that beta-gal II and beta-gal III consist of a common subunit (the bgaA gene product; molecular weight, 120,000), but differ in their assembly (beta-gal II is a dimer, and beta-gal III is a tetramer). The bgaB gene product (molecular weight, 70,000) in Bacillus subtilis harboring pHG5 (a hybrid plasmid consisting of pUB110 and a 2.9-kilobase-pair EcoRI fragment) was estimated to be the beta-gal I protein from its heat stability. Southern hybridization and immunological testing indicated that the two genes have no homology.

Cloning, Molecular↗

Estrogen biosynthesis in human liver--a comparison of aromatase activity for C-19 steroids in fetal liver, adult liver and hepatoma tissues of human subjects.

After incubation of various tritiated C-19 steroids (androstenedione, testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate) with human fetal liver, adult liver and hepatoma tissue homogenates, estrone, estradiol and estriol were analysed after a series of purification steps involving column chromatography, thin layer chromatography and co-crystallization. The findings indicated that the human fetal liver extensively aromatized various C-19 steroids to estrogens, whereas human adult liver and hepatoma tissues exhibited little or no aromatase activities. The formation of estradiol from androstenedione in human fetal liver indicated the presence of 17 beta-hydroxysteroid dehydrogenase in this tissue. It was therefore concluded that although the liver participated in the aromatization process during the fetal stage, extensive aromatization did not take place in the adult liver.

Aged↗

Conjugated oestrogen during the menstrual cycle measured by a direct radioimmunoassay with an antiserum prepared against oestradiol-17-glucosiduronate-[C-6]-BSA conjugate.

Early morning and 24 h urine samples and serum were collected daily throughout the menstrual cycle in women. Urinary oestradiol-17-glucosiduronate (E2-17-G) was measured with a direct radioimmunoassay whose antiserum had been prepared against E2-17-G-[C-6]-bovine serum albumin conjugate and was very specific. On the average, E2-17-G in early morning and 24 h urine samples showed a prominent peak one day before the peak of urinary LH. The time relationship between these urinary E2-17-G and serum E2 levels and peaks was also investigated.

Adult↗

Effects of metal-containing drugs taken simultaneously with clioquinol upon clinical features of SMON.

In order to explore the effects of metals upon the subsequent onset of several clinical events in SMON, a retrospective cohort study was attempted. Study subjects were 216 "exposed" patients and 149 "unexposed" patients. "Exposure" was defined as the simultaneous ingestion of metal-containing drugs with clioquinol before the onset of neurological disorders. These two cohorts were identified from 531 patients among 832 patients, collected by the nationwide survey in 1975 and 1976. Effects provoked by ingestion of five metals (alminum, calcium, magnesium, copper and bismuth) were evaluated by relative risks with and without adjustment of the total amount of clioquinol ingested. Adjusted relative risks were estimated by maximum likelihood method. Significance of relative risk was determined by its 95% confidence interval. Following major findings emerged from the present analysis. (1) Simultaneous ingestion of Al-, Ca-, Mg-, Cu- or Bi-containing drugs with clioquinol significantly reduced the risk of developing motor disturbances. (2) Risk of developing visual disturbances were favorably modified by Al-containing drugs. (3) Clinical severity was significantly reduced by ingestion of Al-, Ca-, Mg- or Bi-containing drugs. (4) About 2-fold increase in risk of unfavorable clinical course was demonstrated by Al-containing drugs. (5) Onset of both green-fur on the tongue and relapse appeared unrelated to the metal-containing drugs ingested. (6) Combined ingestion of two kinds of metal-containing drugs with clioquinol appeared to yield more favorable effects than single ingestion of metal-containing drugs. (7) Al- or Bi-containing drugs demonstrated the strongest association with clinical features of SMON, followed by the drugs containing Mg or Ca. Cu-containing drugs had little association.

Clioquinol↗

[The transfer of cefmenoxime into the retroperitoneal fluid after extensive panhysterectomy].

This study was to investigate the transfer of cefmenoxime (CMX) to the retroperitoneal fluid after extensive panhysterectomy. Twenty-two cases were examined and they were divided into 2 groups, 10 with 1.0 g and 12 with 2.0 g bolus intravenous administration of CMX. In 1.0 g group, CMX concentration in the retroperitoneal fluid was observed 42.0 +/- 9.59 micrograms/ml (Mean +/- S.D.) at 1 hour and thereafter decreased gradually, but it still remained 7.91 +/- 5.18 micrograms/ml at 6 hours after the administration. In 2.0 g group, its concentration was 33.4 +/- 34.5 micrograms/ml at 30 minutes and reached to the peak level of 45.1 +/- 24.6 micrograms/ml at 1 hour and then declined slowly, but it remained 13.3 +/- 8.28 micrograms/ml at 6 hours after the injection. The results demonstrated sufficient transfer of CMX to the retroperitoneal fluid.

Adult↗

[Fundamental and clinical studies on sulbactam/cefoperazone in the field of obstetrics and gynecology].

Fundamental and clinical studies on sulbactam/cefoperazone (SBT/CPZ), a newly developed combined beta-lactam antibiotics, were carried out and the following results were obtained. Each concentration of SBT and CPZ was examined in serum and internal genital organs after single intravenous administration of 2.0 g dose of SBT/CPZ. Each venous serum level of SBT and CPZ was 41.5 micrograms/ml, 122.3 micrograms/ml at 30 minutes after administration respectively. The transfer of SBT and CPZ to internal genital organs was similarly good. Each concentration of SBT and CPZ was examined in serum and retroperitoneal fluid after 1 hour drip infusion of 2.0 g dose of SBT/CPZ. The transfer of SBT and CPZ to retroperitoneal fluid was similarly excellent and the transfer ratio vs. serum level of the former was about 76.2 approximately 321.7%, and the latter was about 27.2 approximately 93.2% respectively. In clinical trial, SBT/CPZ was given to 10 patients with obstetrical and gynecological infections. The efficacy was evaluated as good in 9 patients and poor in 1 patient. As the side effects, diarrhea was appeared in 1 case. In laboratory findings, a transient elevation of serum transaminase was noticed in another one case. From the above results, it was concluded that SBT/CPZ was useful drug for infections in the field of obstetrics and gynecology.

Adult↗

[Fundamental and clinical studies on ceftriaxone in the field of obstetrics and gynecology].

Fundamental and clinical studies on ceftriaxone (CTRX, Ro 13-9904), a new cephalosporin antibiotic, were carried out with the following results. Concentration of CTRX was examined in serum, internal genital organs and retroperitoneal fluid after single intravenous administration of 1.0 g dose. The venous serum level of CTRX was 156 micrograms/ml at 5 minutes after the administration. The favorable transfer of CTRX to internal genital organs and retroperitoneal fluid was demonstrated. In clinical trial, CTRX was given to 10 cases with obstetrical and gynecological infections such as endometritis, adnexitis, pelvic peritonitis and parametritis. The efficacy was evaluated as excellent in 1 case, good in 8 cases and poor in 1 case. No side effects were observed in any of the cases treated with CTRX.

Adult↗